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The big data challenge-and how polypharmacology supports the translation from pre-clinical research into clinical use against neurodegenerative diseases and beyond

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Neural Regeneration Research 2024年第8期19卷 1647-1648页

作者： Sven Marcel Stefan Muhammad Rafehi Drug Development and Chemical Biology Lübeck Institute of Experimental Dermatology(LIED)University of Lübeck and University Medical Center Schleswig-HolsteinLübeckGermany department of pathology Section of NeuropathologyTranslational Neurodegeneration Research and Neuropathology LabUniversity of Oslo and Oslo University HospitalOsloNorway School of Medical Sciences Faculty of Medicine and HealthUniversity of SydneySydneyNSWAustralia Institute of Clinical Pharmacology University Medical Center GöttingenGöttingenGermany department of Medical Education Augsburg University MedicineAugsburgGermany

Introductory comments:The identification and validation of disease-modifying proteins are fundamental aspects in drug ***,the m ultifactority of n eurodegen era tive diseases poses a real challenge for targeted ***,the behavior of individually(over-)expressed to rget proteins in vitro is likely to differ from their actual functional behavior when embedded in cascades and pathways in vivo.

关键词： translation beyond likely

Wildfire severity alters soil microbial exoenzyme production and fungal abundances in the southern Appalachian Mountains

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Pedosphere 2024年第5期34卷 865-878页

作者： Megan L.SCHILL Richard BAIRD Shawn P.BROWN Allison M.VEACH department of Integrative Biology University of Texas at San Antonio Biochemistry Molecular Biology Entomology and Plant Pathology Department Mississippi State University department of Biological Sciences The University of Memphis

Climate change has increased drought frequency and duration that are exacerbated by increased temperatures globally. This effect has, and will continue,to increase fire occurrence across many regions of North America. In the southern Appalachian Mountains, wildfires with high burn severity occurred in 2016due to increased drought and human activity. To investigate the effects of burn severity on soil physicochemical properties, microbial extracellular enzyme production, and microbial abundances in a temperate region, surface soils (0–15 cm) were collected from two sites (the Great Smoky Mountains National Park in Tennessee and the Nantahala National Forest in North Carolina, USA) spanning lightly, moderately, and severely burned areas, accompanied by adjacent unburned locations that act as controls. The soil samples were collected at three time points between 2017 and 2019 (i.e., 0.5, 1, and 2.5 years post-fire)among burn severity plots. Total hydrolytic enzyme production varied over time, with severe burn plots having significantly lower enzyme production at 2.5years post-fire. Individual enzymes varied among burn severities and across time post-fire. Light burn plots showed greater carbon-specific (β-glucosidase and β-xylosidase) and phosphorus-specific (acid phosphatase) enzyme activities at 0.5 years post-fire, but this effect was transient. At 2.5 years post-fire, theβ-xylosidase and acid phosphatase activities were lower in severe or moderate burn plots relative to the controls. In contrast, the activity of nitrogen-specific enzyme leucyl aminopeptidase was the lowest in severe burn plots at 0.5 years post-fire, but was the lowest in light burn plots at 2.5 years post-fire. The fungi:bacteria ratio declined with burn severity, indicating that fungi are sensitive or less resilient to high burn severity during recovery. These results suggest that wildfires alter trajectories for soil microbial structure and function within a 2.5-year timeframe, which potentially

关键词： 16S rRNA burn severity extracellular enzyme fungi:bacteria ratio internal transcribed spacer microbial structure

Cell-type resolved transcriptomic approaches for dissecting selective vulnerability in neurodgeneration

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Neural Regeneration Research 2024年第7期19卷 1411-1413页

作者： Caleb A.Wood Nicholas M.Tran department of Neuroscience Baylor College of MedicineHoustonTXUSA department of molecular and Human Genetics Baylor College of MedicineHoustonTXUSA

A common feature among neurodegenerative conditions is that ce rtain neuronal populations are selectively vulnerable to loss(Fu et al.,2018).By corollary,other neurons are selectively resilient,suggesting they may possess unique features that support their survival.U nderstanding the basis of neuronal resilience or vulnerability would provide a logical strategy to identify factors that could be targeted therapeutically.

关键词： selective targeted

Self-assembly of tau fragments as a key pathologic event in tauopathies

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Neural Regeneration Research 2024年第12期19卷 2565-2566页

作者： Ly Thi Huong Luu Le Jung Hoon Lee Min Jae Lee department of Biochemistry and molecular Biology Seoul National University College of MedicineSeoulKorea

Tau protein is encoded by the microtubuleassociated protein tau(MAPT)gene and stabilizes microtubules in the *** has unique biophysical properties that make it both highly water-soluble and positively *** tau is an intrinsically disordered protein lacking defined secondary structures,it can acquire highly organized-sheet structures and stack into a filamentous inclusion such as a paired helical filament(PHF).

关键词： tau pathologic assembly

CD9 role in proliferation, rejuvenation, and therapeutic applications

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Genes & Diseases 2024年第3期11卷 95-97页

作者： Sai Priyanka Kodam Neda Baghban Mujib Ullah Institutefor Immunityand Transplantation Stem Cell Biology and Regenerative MedicineSchool of MedicineMolecular Medicine Department of MedicineStanford UniversityPaloAltoCA94304USA

The CD9 gene,also known as the Tspan29 gene,codes for a protein called CD9,which is a member of the tetraspanin family of transmembrane proteins.^(1) The CD9 protein is involved in various cellular processes,including cell proliferation,differentiation,adhesion,and migration.^(1,2) CD9 has also been found to play a role in the regulation of stem cell proliferation and differentiation.

关键词： migration. therapeutic CD9

Microbiome changes in esophageal cancer:implications for pathogenesis and prognosis

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Cancer Biology & medicine 2024年第2期21卷 163-174页

作者： Yi Li Bing Wei Xia Xue Hongle Li Jun Li department of molecular pathology Clinical Pathology CenterAffiliated Cancer Hospital of Zhengzhou University and Henan Cancer HospitalZhengzhou 450003China Henan Key Laboratory of molecular pathology Zhengzhou 450003China Henan Key Laboratory of Helicobacter pylori&Microbiota and Gastrointestinal Cancer Marshall Medical Research CenterThe Fifth Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

Esophageal cancer(EC)is an aggressive malignancy with a poor *** factors,including dietary habits,and antacid and antibiotic use,have been shown to influence the esophageal ***,enrichment and diversity of the esophageal microbiome can also impact its *** studies have revealed prevalent changes in the esophageal microbiome among patients with EC,thus suggesting the potential contribution of the esophageal microbiome to EC ***,distinct microbiome compositions have been observed in patients with different responses to radiotherapy and chemotherapy,indicating the role of the esophageal microbiome in modulating treatment *** this review,we have examined previous studies on the esophageal microbiome in healthy individuals and patients with EC or other esophageal diseases,with a focus on identifying microbial communities associated with EC pathogenesis and *** the role of the microbiome in EC may aid in early detection and optimized treatment strategies,ultimately leading to better outcomes for patients.

关键词： Esophageal cancer microbiome dysbiosis microenvironment carcinogenesis

SCFD1 in amyotrophic lateral sclerosis:reconciling a genetic association with in vivo functional analysis

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Neural Regeneration Research 2024年第6期19卷 1201-1202页

作者： Ruben J.Cauchi Centre for molecular medicine and Biobanking Biomedical Sciences BuildingDepartment of Physiology and BiochemistryFaculty of Medicine and SurgeryUniversity of MaltaMsidaMalta

Amyotrophic lateral sclerosis(ALS)is a neurodegenerative disease characterized by progressive loss of upper and lower motor neurons,resulting in muscle weakness and spasticity,eventually leading to death due to respiratory *** by our group of a casecontrol cohort from an isolated island population have found that genetics plays a significant role in disease etiology(Farrugia Wismayer et al.,2023).

关键词： sclerosis respiratory

NLRP3/1-mediated pyroptosis:beneficial clues for the development of novel therapies for Alzheimer’s disease

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Neural Regeneration Research 2024年第11期19卷 2400-2410页

作者： Bo Hu Jiaping Zhang Jie Huang Bairu Luo Xiansi Zeng Jinjing Jia department of pathology and Municipal Key-Innovative Discipline of molecular Diagnostics Jiaxing Hospital of Traditional Chinese MedicineJiaxing UniversityJiaxingZhejiang ProvinceChina Research Center of Neuroscience Jiaxing University Medical CollegeJiaxingZhejiang ProvinceChina department of Clinical pathology Jiaxing University Master Degree Cultivation BaseZhejiang Chinese Medical UniversityJiaxingZhejiang ProvinceChina

The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis,which is a lytic,inflammatory form of cell *** is accumulating evidence that nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3(NLRP3)inflammasome-mediated microglial pyroptosis and NLRP1 inflammasome-mediated neuronal pyroptosis in the brain are closely associated with the pathogenesis of Alzheimer’s *** this review,we summarize the possible pathogenic mechanisms of Alzheimer’s disease,focusing on *** also describe the structures of NLRP3 and NLRP1 and the role their activation plays in Alzheimer’s ***,we examine the neuroprotective activity of small-molecule inhibitors,endogenous inhibitor proteins,microRNAs,and natural bioactive molecules that target NLRP3 and NLRP1,based on the rationale that inhibiting NLRP3 and NLRP1 inflammasome-mediated pyroptosis can be an effective therapeutic strategy for Alzheimer’s disease.

关键词： Alzheimer’s disease caspase-1 GSDMD inflammasome neuroinflammation NLRP1 NLRP3 pyroptosis therapeutic strategies

Microglia out of place—mapping macrophages across the developing human body

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Cellular & molecular Immunology 2024年第3期21卷 210-212页

作者： Roman Sankowski Marco Prinz Institute of neuropathology Faculty of MedicineUniversity of FreiburgFreiburgGermany Signalling Research Centres BIOsS and CIBSs University of FreiburgFreiburgGermany

Macrophages(MΦs)are versatile cells found in every *** the body,they work tirelessly to maintain *** this end,they are instructed by their respective niches to express organ-specific genes and proteins,resulting in a variety of cell morphologies and highly specialized functions across different tissues[1].A recent study by Wang et *** single-cell RNA sequencing to comprehensively profile human MΦphenotypes across 19 organs between postconception weeks(PCW)4 and 26[2].This study revealed a surprising diversity of these cells and suggests new avenues of research.

关键词： organs instru